Interesting Fatty Liver Articles -Spring 2016

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J Bousier et al. Hepatology 2016; 63: 764-75.  This study showed an association between the severity of nonalcoholic fatty liver disease and gut dysbiosis/shift in gut microbiome in 57 patients.  Specifically, Bacteroides was independently associated with NASH and Ruminococcus with significant fibrosis.

V WS Wong et al. Hepatology 2016; 63: 754-63. This study showed that NAFLD (identified by ultrasonography screening) was frequent (58.2%) among 612 consecutive patients who were undergoing coronary angiogram. During a followup (3679 patient-years), NAFLD patients had a lower adjusted HR of death (0.36).  Older age and diabetes were indepenently associated with cardiovascular events.  In addition, during f/u NAFLD patients in their cohort rarely developed liver cancer or cirrhotic complications.  Thus, NAFLD is common among patients with coronary artery disease but did not predict a worsened outcome.

F Piscaglia et al. Hepatology 2016; 63: 827-38. This report was a study of 756 patients with liver cancer (HCC) due to either NAFLD (145) or HCV (611). HCC in NAFLD patients had a larger volume, was more infiltrative, and was detected outside surveillance.  NAFLD-HCC was associated with a lower survival (25.5 months compared with 33.7 months for HCV-HCC). The authors note that after patient matching for tumor stage, the survival rate was similar. The difference in survival does not account for lead-time bias (What’s More Important: Improving Mortality Rate or Survival …).  Overall, the study indicates that without surveillance, HCC is detected later.  Due to the frequency of NAFLD, it is unclear which patients would benefit from surveillance and what type of surveillance should be recommended.

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Farjado, Puerto Rico

Farjado, Puerto Rico

 

Varicella and Zoster Infections in Children with Inflammatory Bowel Disease

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A recent study (DJ Adams, CM Nylund. J Pediatr 2016; 171: 140-5) looked at a large database (1997-2012) with nearly 9 million admissions.  In this retrospective cohort, there were 4434 admissions related to varicella and 4488 due to herpes zoster.

  • Children with Crohn’s disease had a greater increased risk: Varicella OR 12.75, and Zoster OR 7.9 compared to the general population.
  • Children with ulcerative colitis had increased risk compared to general population but less compared to children with Crohn’s disease: Varicella OR 4.25, and Zoster OR 3.9
  • Overall, the risk of these infections improved among all groups over the 15 year study period

One significant limitation of this study is that children with IBD may have been hospitalized more readily out of concern for their vulnerability.  It is noted that there were no deaths due to these infections in the children with IBD.

My take (from the authors):  the increased risk of Varicella and Zoster “were comparable with that observed in children with HIV, malignancy, and primary immune deficiency.”  Given the difficulty of immunizing children on immunosuppressive treatments, at the very least, immunizing household contacts needs to take place.

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Fox Theatre on a Tuesday

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Vitamin D and IBD, More Data

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Another large study (Kabbani TA, et al. Am J Gastroenterol. 2016;doi:10.1038/ajg.2016.53) links low vitamin D status with worse outcomes in IBD.

An excerpt from summary from HealioGastro: (Low vitamin D linked to higher morbidity, disease severity in IBD)

Binion and colleagues identified 965 IBD patients (61.9% Crohn’s disease; 38.1% ulcerative colitis; 52.3% women; mean age, 44 years) with up to 5 years of follow-up data in University of Pittsburgh Medical Center’s longitudinal IBD natural history registry…

At enrollment, 8.9% of patients were vitamin D deficient and 33.1% had vitamin D insufficiency vs. 4.9% and 23.6%, respectively, at the conclusion of the study period. Among patients who received vitamin D supplements, 67.9% achieved normal levels by the end of the study…

Overall, patients with low vitamin D levels required significantly more steroids, biologics, narcotics, computed tomography scans, emergency department visits, hospital admissions and surgeries compared with those who had normal mean vitamin D levels (P < .05). They also had worse pain, disease activity scores and quality of life (P < .05).

“More importantly, correction of vitamin D deficiency was associated with overall improvement in clinical status,” Binion said.

My take: Vitamin D levels are often low when patients are acutely ill and can improve without supplements in many; this accounts for some of the association with worsened outcomes.  True vitamin D deficiency and insufficiency does have negative physiologic effects and should be treated.

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Gibbs Gardens

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John Oliver & Understanding Scientific Studies

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A recent John Oliver segment (~20 minutes) provides a terrific look at how scientific studies need to be evaluated.  Here’s the link: John Oliver Scientific Studies

His main points:

  • Scientists are under pressure to publish and sometimes publish a study with a title to grab interest
  • P-hacking can be done to find statistical significance/correlation that is bogus
  • Reports are often distorted by the media to generate a buzz.  Smelling farts does not prevent cancer (see image below).
  • Some reports extrapolate findings in animals to humans without any studies and without mentioning that these were animal experiments; in addition, most treatments on lab mice do not work for humans.
  • Many media reports do not mention whether the study was industry-funded or the size of the study.  Reports with 10 or 20 people are more likely to lead to false conclusions

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Screen Shot 2016-05-09 at 6.00.08 PM

 

Dreaded Nausea

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One symptom that is dreaded by both patients and physicians is nausea.  A helpful review on this topic (K Kovacic, C DiLorenzo. JPGN 2016; 62: 365-71) provides information on functional nausea.  A few points:

Diagnostic:

  • Endoscopy has low yield.  One cited study suggested that in the absence of clinical alarm symptoms, 98% of endoscopies were normal.
  • 4-hour nuclear medicine study ‘may be justified.’

Therapeutic: Numerous drug/alternative therapies are discussed -most with a paucity of data.  These include:

  • Alternatives agents: Ginger, STW5 (iberogast), peppermint oil
  • Antiemetics: Ondansetron, promethazine, prochlorperazine
  • TCAs: amitriptyline, nortriptyline, imipramine, doxepin
  • SSRIs: citalopram, fluoxetine, paroxetine
  • Anxiolytics: buspirone
  • Tetracyclic antidepressant: mirtazapine
  • Antimigraine: cyprohepatadine, propranolol, topiramate, levetiracetam
  • Prokinetics: erythromycin, metoclopropramide, domperidone
  • Others: fludrocortisone, aprepitant, cannabionids
  • Psychology: “early involvement of a psychologist and emphasis on coping strategies and maintaining functioning with continued school attendance is a primary goal.”

The authors note that retrospective data in children suggest that TCAs have a response rate of ~50% (defined as more than a 50% improvement).  In one study, the mean dose of amitriptyline was 50 mg at bedtime.

In a related study, Madani et al (JPGN 2016; 62: 409-13) describe their experience (retrospective review) using cyproheptadine in children with a range of functional gastrointestinal disorders.  The most common indications were functional abdominal pain (36%), functional dyspepsia (23%), combination disorder (17%) and abdominal migraines (12%).  Overall, they included 151 children and they report 110 (72.8%) had complete symptom improvement; the remainder had either partial or no improvement.  In those who responded, the mean initial dose was 0.14 mg/kg/day; the final mean dose was nearly identical. Adverse effects of sleepiness was reported in 13% and weight gain in 10%.

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Link: Impressive “water swallowing” NEJM video (thanks to Jose Garza for sharing).  In a person who had undergone an esophagogastric bypass as a child.  Still photo below:

NEJM Chest

Will Asymptomatic Patients with “Potential” Celiac Disease Benefit from a Gluten-free Diet?

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A recent study (Volta et al. Clin Gastroenterol Hepatol 2016; 14: 686-93) indicates that those with “potential” celiac disease, who are asymptomatic, are unlikely to benefit from a gluten-free diet.  A useful summary is available on the AGA blog: What Happens to Patients with Markers of Celiac Disease but No Symptoms?

An excerpt:

Celiac disease is an immune-mediated gluten-dependent systemic disorder characterized by serologic and genetic factors and villous atrophy in the small intestine. Although some people test positive for antibodies and carry genetic alleles associated with celiac disease, they have relatively normal or slightly inflamed intestinal mucosa, with no or mild enteropathy. These patients are considered to have potential celiac disease (defined as increased serum levels of antibodies against tissue transglutaminase [tTG] without villous atrophy). They can have gastrointestinal and extra-intestinal symptoms or be completely asymptomatic…

To learn more about progression of potential celiac disease, Umberto Volta et al performed a prospective study to track clinical, serologic, and histologic features of 77 patients. The subjects had normal or slight inflammation of the small intestinal mucosa and were followed for 3 years.

Sixty-one patients had intestinal and extra-intestinal symptoms and 16 were completely asymptomatic at diagnosis…

Gluten withdrawal led to significant clinical improvement in all 61 symptomatic patients.

Of the 16 asymptomatic patients, who were left on the gluten-containing diets, only 1 developed mucosal flattening; levels of anti-endomysial and tTG antibodies fluctuated in 5 of these patients or became undetectable.

My take: In symptomatic patients (but not asymptomatic patients) with potential Celiac disease, a gluten-free diet may be worthwhile.

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Mina Falls, El Junque

Mina Falls, El Junque

NY Times: “Never Diet Again”

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A thought-provoking editorial from the NY Times provides a lot of reasons why dieting to lose weight may be counter-productive.  This editorial comes right after recent reports that many of the most successful “biggest losers” have regained their weight.  Here’s the link. Never Diet Again

Key points:

  • Dieting is not successful in adults, with less than 1% achieving long-term success
  • Our body’s neuroscience has a setpoint for normal weight and when we drop below this, our body deploys a number of mechanisms to regain weight
  • Dieting may result in long-term weight gain
  • Dieting may not improve health

Here a few excerpts:

Setpoint: “When dieters’ weight drops below it, they not only burn fewer calories but also produce more hunger-inducing hormones and find eating more rewarding.”

Diet industry: ” A report for members of the industry stated: “In 2002, 231 million Europeans attempted some form of diet. Of these only 1 percent will achieve permanent weight loss.”

Does dieting increase weight gain? “The causal relationship between diets and weight gain can also be tested by studying people with an external motivation to lose weight. Boxers and wrestlers who diet to qualify for their weight classes presumably have no particular genetic predisposition toward obesity. Yet a 2006 study found that elite athletes who competed for Finland in such weight-conscious sports were three times more likely to be obese by age 60 than their peers who competed in other sports.”

Obesity overrated as cause of mortality: “But our culture’s view of obesity as uniquely deadly is mistaken. Low fitness, smoking, high blood pressure, low income and loneliness are all better predictors of early death than obesity. Exercise is especially important: Data from a 2009 study showed that low fitness is responsible for 16 percent to 17 percent of deaths in the United States, while obesity accounts for only 2 percent to 3 percent, once fitness is factored out.”

My take: This short article explains quite well why obesity is so hard to treat with diet approaches.  Primary prevention of obesity at younger ages along with emphasis on staying active are likely to achieve more than focusing on diet alone.

University of Michigan, Law Quad

University of Michigan, Law Quad

 

538: Gut Science Week

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While FiveThirtyEight garners a lot of attention for its political and sports forecasts, there are often health-related posts.  This week is devoted to Gut Science Week.

Here’s the link: Gut Science Week Introduction

Here’s an excerpt:

One of the major leaps forward in gut science began with an accidental shooting at a trading post on June 6, 1822. A fur trader named Alexis St. Martin took a bullet in the abdomen, leaving him with a hole ripped through his muscle, bone and internal organs…

His doctor, William Beaumont, could literally tie a bit of food on a string, shove it into St. Martin’s stomach through the hole, and pull it back out again. Using this one weird trick, Beaumont extracted samples of the man’s gastric juices. Over eight years and more than 200 awkwardly invasive experiments, St. Martin and Beaumont gave humanity its first real understanding of how digestion works.

Another post: Everybody is Constipated, Nobody is Constipated

Here’s an excerpt:

Doctors use diagnostic criteria for constipation, where patients have to experience two or more of six symptoms:

  1. Straining during at least 25 percent of defecations
  2. Lumpy or hard stools in at least 25 percent of defecations
  3. Sensation of incomplete evacuation in at least 25 percent of defecations
  4. Sense of obstruction in at least 25 percent of defecations
  5. Manual maneuvers needed to facilitate at least 25 percent of defecations
  6. Fewer than three defecations per week

And a video: What Your Poop Says About You — FiveThirtyEight

Gut Science Week --FiveThirtyEight

Gut Science Week –FiveThirtyEight

Parent Perspective, Pediatric Nutritionist and Traci Nagy

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A recent post on The Pediatric Nutritionist blog (Kipp Ellsworth) provides a wealth of useful information for clinicians taking care of children with enteral tubes: Understanding the Parent Perspective: Communicating with Parents and Caregivers about Tube Feeding

The presentation was given by Traci Nagy who founded the FeedingTubeAwareness website, which I have been a big fan for several years.  I probably recommend this website at least once everyday at work.  Of course, I am not the only one familiar with this website which is why it has had more than 200,000 hits last year.

This post includes a 37 slide lecture and links to previous publications.  The “open letter number one” is particularly useful and is reviewed in the slide presentation.  The “open letter number two” also has some useful points, though many would disagree on the utility of testing gastric emptying before fundoplication.

My take: Look at this post -it will help you be a more effective clinician if you take care of kids with enteral tubes.

A few of the slides:

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What Happened to Skepticism re: Lipid Emulsion Position Paper

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A recent position paper (from ESPGHAN) (I Hojsak et al. JPGN 2016; 62: 776-92) made me wonder how different people can look at the same data and come to opposite conclusions.

In short, this article systemically reviews intravenous lipid emulsions and the risk of hepatotoxicity.  The review on the data is quite helpful.  The authors conclude that short-term use of the various emulsions currently in use do not result in a significant difference in neonates, infants and children.

The authors acknowledge that the data for long-term use of these emulsions is limited. They state that “there is evidence indicating that just tailoring and adjusting PN in children on long-term PN could improve liver disease, meaning that the focus should not only be on the type of ILE.”

“Although the quality of data are lacking there is some evidence that the use of multicomponent fish oil-containing ILE may contribute to a decrease” in liver toxicity.

What I don’t understand: The authors recommend: “it appears prudent to use multicomponent FO [fish oil]-containing ILE (GR C)” and literally the next sentence: “The present evidence base is inadequate to determine the optimal strategy for intravenous lipid supply.”

My take: I think we need to gather the data before having official position paper  recommendations.

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